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mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated
Fabio Gelsomino1, Andrea Casadei-Gardini1, Francesco Caputo1
1Department of Oncology and Hematology, University Hospital of Modena, 41124 Modena, Italy.
Background:
Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve.
Methods:
Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed.
Results:
Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature.
Conclusions:
Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting.
Insights
Biomarkers like phosphorylated mTOR and S6K may predict better outcomes for neuroendocrine tumor patients treated with everolimus. This suggests the mTOR pathway activation can guide treatment decisions for NETs.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Research
Background:
- Neuroendocrine tumors (NETs) are treated with everolimus (Eve), a mammalian target of Rapamycin (mTOR) inhibitor.
- Currently, no validated biomarkers predict everolimus efficacy in NET patients.
- This study investigates p-mTOR and p70S6-kinase (S6K) expression as potential predictive biomarkers.
Purpose of the Study:
- To explore the correlation between p-mTOR and p-S6K expression and patient outcomes in NETs treated with everolimus.
- To determine if mTOR pathway activation can serve as a predictive biomarker for everolimus therapy in NETs.
Main Methods:
- Immunohistochemistry was used to assess p-mTOR and p-S6K expression in NET tissue specimens from patients treated with everolimus.
- Patient outcomes, including response rate (RR), progression-free survival (PFS), and overall survival (OS), were analyzed.
- Univariate and multivariate Cox regression analyses were performed to evaluate the predictive value of biomarkers.
Main Results:
- Twenty-four advanced NET patients treated with everolimus were analyzed.
- Eight patients (33.3%) were positive for both p-mTOR and p-S6K.
- Patients with positive biomarker expression showed improved median PFS (18.2 months) and OS (39.9 months) compared to negative patients (13 and 32.4 months, respectively).
Conclusions:
- Activation of the mTOR pathway, indicated by p-mTOR and p-S6K expression, may predict better outcomes in NET patients treated with everolimus.
- These findings suggest potential utility of mTOR pathway biomarkers in guiding everolimus therapy for NETs.
- Further prospective studies are warranted to confirm these results.
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